In vitro antioxidant (spectrophotometric/electrochemical) and enzymatic activities of aniline derivative Schiff base: Experimental and computational assessment

Hereby, the in vitro biological, electrochemical, computational, molecular docking, and in silico ADMET properties of the H₂L ligand have been investigated. The antioxidant potential was evaluated using spectrochemical as well as electrochemical assays. H₂L was found to exhibit intriguing antioxidant capacities in almost several in vitro applications of tests such as DPPH, ABTS, GOR, PRAC, reducing power, CUPRAC, phenanthroline, and the optical properties of silver nanoparticles (SNPs). The H₂L showed scavenging ability against electrochemically generated superoxide anion radical (O₂^·−) by electrochemical reduction of O₂ quantitated in terms of I %. Furthermore, H₂L was tested for some enzymatic inhibition activities (cholinesterase, tyrosinase, urease, and α-amylase), displaying higher inhibition toward these selected enzymes. A theoretical study was carried out by the density functional (DFT) method (gas phase/B3LYP functional associated with the 6–31G (d,p) basis) for thermodynamic behavior, stability, and reactivity prediction. Then, a docking study was performed using AutoDock and MG-tools programs with the same selected proteins with PDB IDs as follows: 4EY7, 4BDS, 2Y9X, 3LA4, and 2QV4, respectively, to visualize the best docked pose and favorable ligand-protein binding interactions. The in silico results revealed that H₂L exhibited stronger tyrosinase inhibitory activity than kojic acid. Thus, these results showed good agreement with the experimental data obtained from the enzyme-inhibiting assay. Finally, several important physicochemical descriptors were examined through in silico ADMET analysis and additionally processed through in vitro PAMPA-BBB permeability assay. Finally, to identify the optimal combinations with the antioxidant responses and based on the results obtained from the response surface methodology (RSM), optimization analyses were also carried out.